Approximately 50% of patients with ERBB2 (which may also be referred to as HER2) positive breast cancer develop cellular and humoral immune response to ERBB2 (Disis et al., 1994). Antibodies are directed both to ectodomains and to intracellular domains of ERBB2. Furthermore, both IgG and IgM anti-ERBB2 has been detected. Higher titers of endogenous Ab anti-ERBB2 ECD are present in earlier breast cancer clinical stages (Disis et al., 1997). In fact, spontaneous immune responses to all members of the ERBB family (EGFR, ERBB2, ERBB3, ERBB4) have been detected (Bei et al., 1999). Also, little is known about the effects of the endogenous antibodies on phosphorylation of ERBB2 and its downstream signaling. T cell proliferation assays also show reactivity to ERBB2 epitopes, but the meaning of this response is unknown as well.
According to the immune network hypothesis, if there is an immune response with antibody (Ab1) production, there will be a regulatory response, with production of another antibody (Ab2) directed to Ab1. Little is known about the presence of endogenous Ab directed to anti-HER2 Abs in subjects, or their potential impact on disease or treatments.